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1.
Clin Transl Med ; 14(3): e1632, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38515278

RESUMO

INTRODUCTION: Despite considerable therapeutic advances in the last 20 years, metastatic cancers remain a major cause of death. We previously identified prominin-2 (PROM2) as a biomarker predictive of distant metastases and decreased survival, thus providing a promising bio-target. In this translational study, we set out to decipher the biological roles of PROM2 during the metastatic process and resistance to cell death, in particular for metastatic melanoma. METHODS AND RESULTS: Methods and results: We demonstrated that PROM2 overexpression was closely linked to an increased metastatic potential through the increase of epithelial-to-mesenchymal transition (EMT) marker expression and ferroptosis resistance. This was also found in renal cell carcinoma and triple negative breast cancer patient-derived xenograft models. Using an oligonucleotide anti-sense anti-PROM2, we efficaciously decreased PROM2 expression and prevented metastases in melanoma xenografts. We also demonstrated that PROM2 was implicated in an aggravation loop, contributing to increase the metastatic burden both in murine metastatic models and in patients with metastatic melanoma. The metastatic burden is closely linked to PROM2 expression through the expression of EMT markers and ferroptosis cell death resistance in a deterioration loop. CONCLUSION: Our results open the way for further studies using PROM2 as a bio-target in resort situations in human metastatic melanoma and also in other cancer types.


Assuntos
Ferroptose , Melanoma , Humanos , Animais , Camundongos , Ferroptose/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Glicoproteínas de Membrana
2.
APL Bioeng ; 8(1): 016113, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38445236

RESUMO

Osteosarcoma (OS) is a rare form of primary bone cancer, impacting approximately 3.4 × 106 individuals worldwide each year, primarily afflicting children. Given the limitations of existing cancer therapies, the emergence of nanotheranostic platforms has generated considerable research interest in recent decades. These platforms seamlessly integrate therapeutic potential of drug compounds with the diagnostic capabilities of imaging probes within a single construct. This innovation has opened avenues for enhanced drug delivery to targeted sites while concurrently enabling real-time monitoring of the vehicle's trajectory. In this study, we developed a nanotheranostic system employing the layer-by-layer (LbL) technique on a core containing doxorubicin (DOXO) and in-house synthesized carbon quantum dots. By utilizing chitosan and chondroitin sulfate as polyelectrolytes, we constructed a multilayered coating to encapsulate DOXO and docetaxel, achieving a coordinated co-delivery of both drugs. The LbL-functionalized nanoparticles exhibited an approximate size of 150 nm, manifesting a predominantly uniform and spherical morphology, with an encapsulation efficiency of 48% for both drugs. The presence of seven layers in these systems facilitated controlled drug release over time, as evidenced by in vitro release tests. Finally, the impact of the LbL-functionalized nanoparticles was evaluated on U2OS and Saos-2 osteosarcoma cells. The synergistic effect of the two drugs was found to be crucial in inducing cell death, particularly in Saos-2 cells treated with nanoparticles at concentrations higher than 10 µg/ml. Transmission electron microscopy analysis confirmed the internalization of the nanoparticles into both cell types through endocytic mechanisms, revealing an underlying mechanism of necrosis-induced cell death.

3.
Food Chem ; 448: 139057, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38555694

RESUMO

Kakadu plum (Terminalia ferdinandiana) (KP) is an indigenous fruit used as a functional ingredient in powdered form. Three KP doses (1, 2.5 and 5 g) were digested in a dynamic in vitro gut digestion model over 48 h. Faecal water digests from the colonic reactors were assessed for total soluble polyphenols (TSP), ferric reducing antioxidant power (FRAP), phenolic metabolites and short-chain fatty acids (SCFAs). Effects of digests on cell viability were tested against Caco-2 intestinal and HepG2 hepatic cells. All doses of KP fermentation produced castalagin, corilagin, chebulagic acid, chebulinic acid, and gallic acid. TSP and FRAP significantly increased in 5 g KP digests at 0 and 48 h of fermentation. SCFA concentrations significantly increased after 48 h. Cytotoxic effects of 2.5 and 5 g KP digests diminished significantly after 12 h. Overall, colonic fermentation increased antioxidant activity and polyphenolic metabolites of 5 g KP powder for 48 h.

4.
J Med Microbiol ; 73(1)2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38235783

RESUMO

Introduction. Helicobacter pylori infection is a major global health concern, linked to the development of various gastrointestinal diseases, including gastric cancer. To study the pathogenesis of H. pylori and develop effective intervention strategies, appropriate animal pathogen models that closely mimic human infection are essential.Gap statement. This study focuses on the understudied hpEastAsia genotype in Southeast Asia, a region marked by a high H. pylori infection rate. No mouse-adapted model strains has been reported previously. Moreover, it recognizes the urgent requirement for vaccines in developing countries, where overuse of antimicrobials is fuelling the emergence of resistance.Aim. This study aims to establish a novel mouse-adapted H. pylori model specific to the hpEastAsia genotype prevalent in Southeast Asia, focusing on comparative genomic and histopathological analysis of pathogens coupled with vaccine preclinical studies.Methodology. We collected and sequenced the whole genome of clinical strains of H. pylori from infected patients in Vietnam and performed comparative genomic analyses of H. pylori strains in Southeast Asia. In parallel, we conducted preclinical studies to assess the pathogenicity of the mouse-adapted H. pylori strain and the protective effect of a new spore-vectored vaccine candidate on male Mlac:ICR mice and the host immune response in a female C57BL/6 mouse model.Results. Genome sequencing and comparison revealed unique and common genetic signatures, antimicrobial resistance genes and virulence factors in strains HP22 and HP34; and supported clarithromycin-resistant HP34 as a representation of the hpEastAsia genotype in Vietnam and Southeast Asia. HP34-infected mice exhibited gastric inflammation, epithelial erosion and dysplastic changes that closely resembled the pathology observed in human H. pylori infection. Furthermore, comprehensive immunological characterization demonstrated a robust host immune response, including both mucosal and systemic immune responses. Oral vaccination with candidate vaccine formulations elicited a significant reduction in bacterial colonization in the model.Conclusion. Our findings demonstrate the successful development of a novel mouse-adapted H. pylori model for the hpEastAsia genotype in Vietnam and Southeast Asia. Our research highlights the distinctive genotype and pathogenicity of clinical H. pylori strains in the region, laying the foundation for targeted interventions to address this global health burden.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Vacinas , Humanos , Masculino , Feminino , Camundongos , Animais , Infecções por Helicobacter/microbiologia , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Genótipo , Genômica , Sudeste Asiático/epidemiologia
5.
RSC Chem Biol ; 4(12): 1096-1110, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38033728

RESUMO

DAXX (Death Domain Associated Protein 6) is frequently upregulated in various common cancers, and its suppression has been linked to reduced tumor progression. Consequently, DAXX has gained significant interest as a therapeutic target in such cancers. DAXX is known to function in several critical biological pathways including chromatin remodelling, transcription regulation, and DNA repair. Leveraging structural information, we have designed and developed a novel set of stapled/stitched peptides that specifically target a surface on the N-terminal helical bundle domain of DAXX. This surface serves as the anchor point for binding to multiple interaction partners, such as Rassf1C, p53, Mdm2, and ATRX, as well as for the auto-regulation of the DAXX N-terminal SUMO interaction motif (SIM). Our experiments demonstrate that these peptides effectively bind to and inhibit DAXX with a higher affinity than the known interaction partners. Furthermore, these peptides release the auto-inhibited SIM, enabling it to interact with SUMO-1. Importantly, we have developed stitched peptides that can enter cells, maintaining their intracellular concentrations at nanomolar levels even after 24 hours, without causing any membrane perturbation. Collectively, our findings suggest that these stitched peptides not only serve as valuable tools for probing the molecular interactions of DAXX but also hold potential as precursors to the development of therapeutic interventions.

6.
Circulation ; 148(5): 405-425, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37409482

RESUMO

BACKGROUND: Adeno-associated virus (AAV) has emerged as one of the best tools for cardiac gene delivery due to its cardiotropism, long-term expression, and safety. However, a significant challenge to its successful clinical use is preexisting neutralizing antibodies (NAbs), which bind to free AAVs, prevent efficient gene transduction, and reduce or negate therapeutic effects. Here we describe extracellular vesicle-encapsulated AAVs (EV-AAVs), secreted naturally by AAV-producing cells, as a superior cardiac gene delivery vector that delivers more genes and offers higher NAb resistance. METHODS: We developed a 2-step density-gradient ultracentrifugation method to isolate highly purified EV-AAVs. We compared the gene delivery and therapeutic efficacy of EV-AAVs with an equal titer of free AAVs in the presence of NAbs, both in vitro and in vivo. In addition, we investigated the mechanism of EV-AAV uptake in human left ventricular and human induced pluripotent stem cell-derived cardiomyocytes in vitro and mouse models in vivo using a combination of biochemical techniques, flow cytometry, and immunofluorescence imaging. RESULTS: Using cardiotropic AAV serotypes 6 and 9 and several reporter constructs, we demonstrated that EV-AAVs deliver significantly higher quantities of genes than AAVs in the presence of NAbs, both to human left ventricular and human induced pluripotent stem cell-derived cardiomyocytes in vitro and to mouse hearts in vivo. Intramyocardial delivery of EV-AAV9-sarcoplasmic reticulum calcium ATPase 2a to infarcted hearts in preimmunized mice significantly improved ejection fraction and fractional shortening compared with AAV9-sarcoplasmic reticulum calcium ATPase 2a delivery. These data validated NAb evasion by and therapeutic efficacy of EV-AAV9 vectors. Trafficking studies using human induced pluripotent stem cell-derived cells in vitro and mouse hearts in vivo showed significantly higher expression of EV-AAV6/9-delivered genes in cardiomyocytes compared with noncardiomyocytes, even with comparable cellular uptake. Using cellular subfraction analyses and pH-sensitive dyes, we discovered that EV-AAVs were internalized into acidic endosomal compartments of cardiomyocytes for releasing and acidifying AAVs for their nuclear uptake. CONCLUSIONS: Together, using 5 different in vitro and in vivo model systems, we demonstrate significantly higher potency and therapeutic efficacy of EV-AAV vectors compared with free AAVs in the presence of NAbs. These results establish the potential of EV-AAV vectors as a gene delivery tool to treat heart failure.


Assuntos
Vesículas Extracelulares , Células-Tronco Pluripotentes Induzidas , Humanos , Camundongos , Animais , Dependovirus/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Vetores Genéticos , Células-Tronco Pluripotentes Induzidas/metabolismo , Anticorpos Neutralizantes , Vesículas Extracelulares/metabolismo
7.
Curr Med Imaging ; 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37132318

RESUMO

BACKGROUND: Deep learning-based diagnosis systems are useful to identify abnormalities in medical images with the greatly increased workload of doctors. Specifically, the rate of new cases and deaths from malignancies is rising for liver diseases. Early detection of liver lesions plays an extremely important role in effective treatment and gives a higher chance of survival for patients. Therefore, automatic detection and classification of common liver lesions are essential for doctors. In fact, radiologists mainly rely on Hounsfield Units to locate liver lesions but previous studies often pay little attention to this factor. METHODS: In this paper, we propose an improved method for the automatic classification of common liver lesions based on deep learning techniques and the variation of Hounsfield Unit densities on CT images with and without contrast. Hounsfield Unit is used to locate liver lesions accurately and support data labeling for classification. We construct a multi-phase classification model developed on the deep neural networks of Faster R-CNN, R-FCN, SSD, and Mask R-CNN with the transfer learning approach. RESULTS: The experiments are conducted on six scenarios with multi-phase CT images of common liver lesions. Experimental results show that the proposed method improves the detection and classification of liver lesions compared with recent methods because its accuracy achieves up to 97.4%. CONCLUSION: The proposed models are very useful to assist doctors in the automatic segmentation and classification of liver lesions to solve the problem of depending on the clinician's experience in the diagnosis and treatment of liver lesions.

8.
Nucleic Acids Res ; 51(9): 4148-4177, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37094040

RESUMO

DNA sequence composition determines the topology and stability of G-quadruplexes (G4s). Bulged G-quadruplex structures (G4-Bs) are a subset of G4s characterized by 3D conformations with bulges. Current search algorithms fail to capture stable G4-B, making their genome-wide study infeasible. Here, we introduced a large family of computationally defined and experimentally verified potential G4-B forming sequences (pG4-BS). We found 478 263 pG4-BS regions that do not overlap 'canonical' G4-forming sequences in the human genome and are preferentially localized in transcription regulatory regions including R-loops and open chromatin. Over 90% of protein-coding genes contain pG4-BS in their promoter or gene body. We observed generally higher pG4-BS content in R-loops and their flanks, longer genes that are associated with brain tissue, immune and developmental processes. Also, the presence of pG4-BS on both template and non-template strands in promoters is associated with oncogenesis, cardiovascular disease and stemness. Our G4-BS models predicted G4-forming ability in vitro with 91.5% accuracy. Analysis of G4-seq and CUT&Tag data strongly supports the existence of G4-BS conformations genome-wide. We reconstructed a novel G4-B 3D structure located in the E2F8 promoter. This study defines a large family of G4-like sequences, offering new insights into the essential biological functions and potential future therapeutic uses of G4-B.


Assuntos
Quadruplex G , Humanos , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Regiões Promotoras Genéticas , Sequência de Bases
9.
Phys Chem Chem Phys ; 25(13): 9073-9082, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36919786

RESUMO

Beryllium is a vital alkaline-earth metal for plasma physics, space science, and nuclear technology. Unfortunately, its accurate phase diagram is clouded by many controversial results, even though solid beryllium can only exist with hcp or bcc crystalline structures. Herein, we offer a simple quantum-statistical solution to the above problem. Our core idea is to develop the moment expansion technique to determine the Helmholtz free energy under extreme conditions. This strategy helps elucidate the underlying correlation among symmetric characteristics, vibrational excitations, and physical stabilities. In particular, our analyses reveal that the appearance of anharmonic effects forcefully straightens up the hcp-bcc boundary. This phenomenon explains why it has been difficult to detect bcc signatures via diamond-anvil-cell measurements. Besides, we modify the work-heat equivalence principle to quickly obtain the high-pressure melting profile from the room-temperature equation of state. The hcp-bcc-liquid triple point of beryllium is found at 165 GPa and 4559 K. Our theoretical findings agree excellently with cutting-edge ab initio simulations adopting the phonon quasiparticle method and the thermodynamic integration. Finally, we consider the principal Hugoniot curve and its secondary branches to explore the behaviors of beryllium under shock compression. Our predictions would be advantageous for designing inertial-confinement-fusion experiments.

10.
Foods ; 12(3)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36766151

RESUMO

Tasmannia lanceolata, Diploglottis bracteata and Syzygium aqueum are understudied native Australian plants. This study aimed to characterise the non-anthocyanin phenolic and organic acid profiles of the aqueous extracts obtained from the leaves of T. lanceolata and fruits of D. bracteata and S. aqueum by UHPLC-Q-Orbitrap-MS/MS and UHPLC-TQ-MS/MS. A total of 39, 22, and 27 non-anthocyanin polyphenols were tentatively identified in T. lanceolata, D. bracteata, and S. aqueum extracts, respectively. Furthermore, sugars and ascorbic acid contents as well as in vitro antioxidant and antimicrobial activities of the extracts were determined. Response surface methodology was applied to achieve an extract blend with a strong inhibitory effect against Pseudomonas viridiflava, the main cause of soft rot in vegetables, Bacillus subtilis, Rhodotorula diobovata and Alternaria alternata. The identified compounds including organic acids (e.g., quinic, citric and malic acids) and polyphenols (e.g., catechin, procyanidins, and ellagitannins) might contribute to the observed antimicrobial activity. Furthermore, this study provides the most comprehensive phenolic profiles of these three underutilised native Australian plants to date.

11.
Gene Expr Patterns ; 47: 119289, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574537

RESUMO

The early sign detection of liver lesions plays an extremely important role in preventing, diagnosing, and treating liver diseases. In fact, radiologists mainly consider Hounsfield Units to locate liver lesions. However, most studies focus on the analysis of unenhanced computed tomography images without considering an attenuation difference between Hounsfield Units before and after contrast injection. Therefore, the purpose of this work is to develop an improved method for the automatic detection and classification of common liver lesions based on deep learning techniques and the variations of the Hounsfield Units density on computed tomography scans. We design and implement a multi-phase classification model developed on the Faster Region-based Convolutional Neural Networks (Faster R-CNN), Region-based Fully Convolutional Networks (R-FCN), and Single Shot Detector Networks (SSD) with the transfer learning approach. The model considers the variations of the Hounsfield Unit density on computed tomography scans in four phases before and after contrast injection (plain, arterial, venous, and delay). The experiments are conducted on three common types of liver lesions including liver cysts, hemangiomas, and hepatocellular carcinoma. Experimental results show that the proposed method accurately locates and classifies common liver lesions. The liver lesions detection with Hounsfield Units gives high accuracy of 100%. Meanwhile, the lesion classification achieves an accuracy of 95.1%. The promising results show the applicability of the proposed method for automatic liver lesions detection and classification. The proposed method improves the accuracy of liver lesions detection and classification compared with some preceding methods. It is useful for practical systems to assist doctors in the diagnosis of liver lesions. In our further research, an improvement can be made with big data analysis to build real-time processing systems and we expand this study to detect lesions from all parts of the human body, not just the liver.


Assuntos
Aprendizado Profundo , Neoplasias Hepáticas , Humanos , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Imageamento por Ressonância Magnética
12.
Chem Commun (Camb) ; 58(80): 11264-11267, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36112098

RESUMO

G-quadruplexes (G4s) are attractive anticancer targets. While right-handed G4s have been extensively investigated with many specific ligands reported, left-handed G4s formed by natural DNA have been recently discovered. Here we show that ligands specific for right-handed G4s, such as Phen-DC3 and RHAU peptide, do not bind specifically to left-handed G4s. In right-handed G4s, these ligands can displace capping overhangs and/or loops to stack on the exposed terminal tetrads. In contrast, the presence of tight T-capping in left-handed G4s hinders access to the tetrads.


Assuntos
Quadruplex G , DNA/genética , Ligantes , Peptídeos/genética
13.
Front Nutr ; 9: 961679, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967775

RESUMO

Terminalia ferdinandiana Exell., also known as Kakadu plum, is a wild-harvested native Australian fruit with limited information on how maturity is affecting the phytonutritional properties and bioactivities of the fruit. Thus, this study investigated changes in hydrolysable tannins, phenolic acids, sugar profile, standard physicochemical parameters, and antioxidant-scavenging capacity of wild-harvested Kakadu plum fruits at four different maturity stages, from immature to fully mature. Fruits harvested <25, 25-50, 50-75, and 75-100% degree of fullness were classified as highly immature (stage 1), immature (stage 2), semi-mature (stage 3), and fully mature (stage 4), respectively. Results showed that chebulagic acid, geraniin, chebulinic acid, castalagin, punicalagin, and gallic acid continuously decreased during fruit maturity, while elaeocarpusin, helioscopin B, corilagin, 3,4,6-tri-O-galloyl-S-glucose, and ellagic acid increased at the beginning of fruit growth (from stage 1 to 2), but decreased when the fruits reached their full maturity (stage 4). The levels of hydrolysable tannins and phenolic acids in fully mature fruits (stage 4) were significantly (p ≤ 0.05) lower than that in their immature counterparts (stages 1 and 2). Total phenolic content (TPC) and DPPH antioxidant radical-scavenging activity did not vary significantly between different maturity stages. Pearson's correlation coefficient test indicated that TPC and DPPH positively (p ≤ 0.05) correlate with most of the studied tannin compounds. Sugars (glucose, fructose, and sucrose), total soluble solid content, and titratable acidity increased during the fruit development. Furthermore, principal component analysis (PCA) revealed the difference between the immature and mature samples, based on their nutritional profile and bioactive compounds. The PCA results also suggested a considerable variability between the individual trees, highlighting the challenges of wild-harvest practice.

14.
Cell Prolif ; 55(9): e13255, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35851970

RESUMO

INTRODUCTION: Acute Myeloid Leukaemia (AML) is the most common blood cancer in adults. Although 2 out of 3 AML patients go into total remission after chemotherapies and targeted therapies, the disease recurs in 60%-65% of younger adult patients within 3 years after diagnosis with a dramatically decreased survival rate. Therapeutic oligonucleotides are promising treatments under development for AML as they can be designed to silence oncogenes with high specificity and flexibility. However, there are not many well validated approaches for safely and efficiently delivering oligonucleotide drugs. This issue could be resolved by utilizing a new generation of delivery vehicles such as extracellular vesicles (EVs). METHODS: In this study, we harness red blood cell-derived EVs (RBCEVs) and engineer them via exogenous drug loading and surface functionalization to develop an efficient drug delivery system for AML. Particularly, EVs are designed to target CD33, a common surface marker with elevated expression in AML cells via the conjugation of a CD33-binding monoclonal antibody onto the EV surface. RESULTS: The conjugation of RBCEVs with the CD33-binding antibody significantly increases the uptake of RBCEVs by CD33-positive AML cells, but not by CD33-negative cells. We also load CD33-targeting RBCEVs with antisense oligonucleotides (ASOs) targeting FLT3-ITD or miR-125b, 2 common oncogenes in AML, and demonstrate that the engineered EVs improve leukaemia suppression in in vitro and in vivo models of AML. CONCLUSION: Targeted RBCEVs represent an innovative, efficient, and versatile delivery platform for therapeutic ASOs and can expedite the clinical translation of oligonucleotide drugs for AML treatments by overcoming current obstacles in oligonucleotide delivery.


Assuntos
Vesículas Extracelulares , Leucemia Mieloide Aguda , MicroRNAs , Adulto , Anticorpos Monoclonais/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Oligonucleotídeos Antissenso/uso terapêutico , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/uso terapêutico
15.
ACS Omega ; 6(40): 26130-26139, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34660973

RESUMO

Cellulosic aerogel from water hyacinth (WH) was synthesized to address the dual environmental issues of water hyacinth pollution and the production of a green material. Raw WH was treated with sodium hydroxide (NaOH) with microwave assistance and in combination with hydrogen peroxide (H2O2). The results from X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM) showed that lignin and hemicellulose were markedly decreased after treatment, reducing from 24.02% hemicellulose and 5.67% lignin in raw WH to 8.32 and 1.92%, respectively. Cellulose aerogel from the pretreated WH had a high porosity of 98.8% with a density of 0.0162 g·cm-3 and a low thermal conductivity of 0.030 W·m-1·K-1. After modification with methyl trimethoxysilane (MTMS) to produce a highly hydrophobic material, WH aerogel exhibited high stability for oil absorption at a capacity of 43.3, 43.15, 40.40, and 41.88 (g·g-1) with diesel oil (DO), motor oil (MO), and their mixture with water (DO + W and MO + W), respectively. The adsorption remained stable after 10 cycles.

16.
ACS Appl Mater Interfaces ; 13(33): 40002-40012, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34382786

RESUMO

Although inhibiting hydrate formation in hydrocarbon-water systems is paramount in preventing pipe blockage in hydrocarbon transport systems, the molecular mechanisms responsible for antiagglomerant (AA) performance are not completely understood. To better understand why macroscopic performance is affected by apparently small changes in the AA molecular structure, we perform molecular dynamics simulations. We quantify the cohesion energy between two gas hydrate nanoparticles dispersed in liquid hydrocarbons in the presence of different AAs, and we achieve excellent agreement against experimental data obtained at high pressure using the micromechanical force apparatus. This suggests that the proposed simulation approach could provide a screening method for predicting, in silico, the performance of new molecules designed to manage hydrates in flow assurance. Our results suggest that entropy and free energy of solvation of AAs, combined in some cases with the molecular orientation at hydrate-oil interfaces, are descriptors that could be used to predict performance, should the results presented here be reproduced for other systems as well. These insights could help speed up the design of new AAs and guide future experiments.

17.
Mol Genet Genomic Med ; 9(8): e1732, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34114358

RESUMO

BACKGROUND: X-linked hyper-IgM syndrome (XHIGM) is a rare primary immunodeficiency caused by CD40 ligand defects. METHODS: We identified three patients with XHIGM in Ho Chi Minh City, Vietnam. Whole-exome sequencing, immunological analyses and western blot were performed to investigate phenotypic and genotypic features. RESULTS: Despite showing symptoms typical of XHIGM, including recurrent sinopulmonary infections, oral ulcers and otitis media, the diagnosis was significantly delayed. One patient developed anti-phospholipid syndrome, which has been documented for the first time in XHIGM syndrome. Two patients had elevated IgM levels and all of them had low IgG levels. Exome sequencing revealed mutations in the CD40LG gene: one novel splicing mutation c.156+2T>A and two previously characterised mutations (non-frameshift deletion c.436_438delTAC, stop-gain c.654C>A). Due to these mutations, the CD40 ligand was not expressed in any of the three patients, as demonstrated by western blot analysis. CONCLUSION: This is the first report of XHIGM syndrome in Vietnam indicates that an effective diagnostic strategy, such as sequencing analysis, contributes to reliable diagnosis and subsequent therapy.


Assuntos
Síndrome Antifosfolipídica/genética , Ligante de CD40/genética , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Fenótipo , Adolescente , Adulto , Síndrome Antifosfolipídica/etiologia , Síndrome Antifosfolipídica/patologia , Criança , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/patologia , Masculino , Mutação
18.
Chem Commun (Camb) ; 57(45): 5507-5510, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34036975

RESUMO

Joining peptides and oligonucleotides offers potential benefits, but current methods remain laborious. Here we present a novel approach towards enzymatic ligation of the two modalities through the development of tag phosphoramidites as adaptors that can be readily incorporated onto oligonucleotides. This simple and highly efficient approach paves the way towards streamlined development and production of peptide/protein-oligonucleotide conjugates.


Assuntos
Aminoaciltransferases/química , Proteínas de Bactérias/química , Cisteína Endopeptidases/química , Oligonucleotídeos/química , Peptídeos/química , Proteínas/química , Sequência de Aminoácidos , Sequência de Bases , Compostos Organofosforados/química , Técnicas de Síntese em Fase Sólida
19.
Appl Spectrosc ; 75(7): 834-838, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33464155

RESUMO

In recent years, the native food industry in Australia has increased in both value and volume due to the discovery of a wide range of phytochemicals (e.g., vitamin C, polyphenols) that have potential health benefits. Thus, plant organs and tissues of these native plants are used in a wide range of applications. In particular, the kernel of a native plum, the Kakadu plum (Terminalia ferdinandiana, Combretaceae) is considered to be rich in lipids and other phytochemical compounds. The aim of this study was to evaluate the use of NIR spectroscopy to analyze and characterize kernel samples and tissues of wild harvest fruit samples. The Fourier transform near-infrared reflectance spectra of cracked kernels, seeds cover tissues, and dry powder Kakadu plum kernels were acquired. Both principal component analysis and partial least squares discriminant analysis were used to analyze and interpret the spectral data. A correct classification rate of 93%, 86%, and 80% was achieved for the identification of kernel provenance using all tissues, seed coats, and the whole nuts, respectively. The results of this study reported for the first time the analysis of Kakadu plum kernels and their tissues using NIR spectroscopy.


Assuntos
Prunus domestica , Terminalia , Ácido Ascórbico , Frutas , Espectroscopia de Luz Próxima ao Infravermelho
20.
Front Nutr ; 7: 576532, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304915

RESUMO

Underutilized or traditional leafy vegetables are grown in the wild and cultivated. They are consumed as nutritional accompaniments to staples, either raw (fresh), cooked, or in a dried form, through custom, habit, and tradition. These traditional leafy vegetables are natural rich sources of phytochemicals and nutritional compounds. Over time, the keenness for consumption of traditional vegetables has become less popular. Poor nutrient diets are the main cause of mortality and morbidity, especially in developing countries, where the problem is predominant due to poverty. Consumption of traditional vegetables can assist in the prevention of chronic disease development, as they contain various bioactive compounds that exhibit multiple health benefits. Traditional leafy vegetables play a vital role in combatting hunger, food insecurity, and malnutrition, and most are suitable for food intervention programs. African nightshade (Solanum family) is one such commonly consumed traditional leafy vegetable. During dry seasons, communities often face shortages of vegetables; thus, the preservation of edible leaves is one strategy to help overcome this problem. The adoption of solar drying and fermentation are traditional methods to extend the availability of African nightshade vegetables. Additionally, the agronomy practices and postharvest processing methods affect the phytochemicals and nutritional compounds of African nightshade accessions. This mini-review provides information on changes in phytochemicals, nutrition, and antinutritive compounds with different postharvest processing methods and irrigation. The review provides the justification to promote the cultivation for consumption, by identifying the potential African nightshade accessions that are rich in phytonutritional compounds. This mini-review summarizes and discusses the major information on (i) the micro- and macronutrients present in Solanum retroflexum, the most commonly consumed nightshade species compared with other traditional vegetables in Southern Africa, (ii) the composition of phytochemical compounds present in different nightshade accessions, (iii) the impact of irrigation on phytochemical composition in different nightshade species, and (iv) the impact of postharvest processing on phytochemicals and antinutritive compounds in S. retroflexum. Inclusion of African nightshade, especially S. retroflexum, with the main staple foods can improve protein, iron, and calcium levels in daily diets, which will help to improve people's health and well-being.

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